This invention relates to antibiotic compositions suitable for pharmaceutical use. More particularly, it relates to chlortetracycline solutions containing 2-pyrrolidone.
Previous efforts made to prepare high concentration chlortetracycline solutions have been unsuccessful. This is of particular importance in the case of veterinary parenteral compositions for administration to large animals.
Japanese Patent Publication No. Sho 47-303 discloses stable aqueous solutions of p-biphenylmethyl (dl-tropyl-.alpha.-tropinium) bromide, 2.5%, in which 2-pyrrolidone is present in a concentration of 20%. The use of polyvinylpyrrolidone at a concentration of 30% is also disclosed. The pH of these solutions is less than 7, the preferred range being 3-4.
Japanese Patent Publication No. Sho 43-1758 discloses insecticidal solutions containing hexachlorcyclohexane in alcohol and 2-pyrrolidone as solvents. The use of N-methyl pyrrolidone as a co-solvent is also disclosed.
British Patent Specification No. 802,111 discloses pesticidal compositions containing 2-pyrrolidone or N-methyl pyrrolidone as solvents for DDT, dieldrin, aldrin and similar insecticides. The use of 67-82% of 2-pyrrolidone is exemplified.
British Patent Specification No. 805,026 discloses the use of N-methyl pyrrolidone in concentrations of 40% as a solvent for various medicaments intended for parenteral administration, such as chloramphenicol, N,N'-dibenzyl ethylenediamine-dipenicillin G and procaine penicillin.
U.S. Pat. No. 2,987,437 discloses nematocidal compositions of 3,4-dichlorotetrahydrothiophene, 1,1-dioxide in 2-pyrrolidone.
German Pat. No. 1,091,287 discloses stable aqueous solutions of tyrothricin 0.25% or subtilin 0.2% for nasal or otic use prepared with the aid of pyrrolidione and/or polyvinylpyrrolidone as solubilizers. Pyrrolidone is used in a concentration of 0.5% and polyvinylpyrrolidone can be used up to 10%.
U.S. Pat. No. 3,062,717 discloses aqueous parenteral solutions of tetracycline calcium complexes containing 35-80% of an amide of acetic or lactic acid, such as N,N-dimethylacetamide or N-(.beta.-hydroxyethyl) lactamide, at a pH of 7 to 9.5. Concentrations of 10 to 100 mg/ml are disclosed.
J. Pharm. Sci. 46, p. 458 (1957) discloses that oxytetracycline forms soluble complexes with N-methyl pyrrolidone in aqueous solution. The degree of interaction is limited by pH and solubility considerations.
U.S. Patent Application Ser. No. 646,295, now U.S. Pat. No. 4,018,889 discloses oxytetracycline solutions containing from about 1 to 40 percent oxytetracycline in an aqueous vehicle containing from about 10 to 50 percent by weight of 2-pyrrolidone, about 0.8 to 1.3 molar proportions of a pharmaceutically acceptable magnesium compound soluble in the said solution, said solution having a pH value in the range of from about 7.5 to 9.5.